doi: 10.2169/internalmedicine.

4437-20
Intern Med Advance Publication
http://internmed.jp

【 CASE REPORT 】

Esophageal Ulcers Associated with Ulcerative Colitis:

A Case Series and Literature Review

Kentaro Tominaga 1, Atsunori Tsuchiya 1, Hiroki Sato 1, Takeshi Mizusawa 1, Shinichi Morita 2,
Yui Ishii 1, Nobutaka Takeda 1, Kazuki Natsui 1, Yuzo Kawata 1, Naruhiro Kimura 1,
Yoshihisa Arao 1, Kazuya Takahashi 1, Kazunao Hayashi 1, Junji Yokoyama 1 and Shuji Terai 1

Abstract:
Ulcerative colitis, a chronic and recurrent inflammatory disease, is localized to the colonic mucosa but can
affect other organs and lead to various complications. Gastroduodenitis associated with ulcerative colitis has
been reported. However, little is known about esophageal ulcers. We herein report two rare cases of esopha-
geal ulcers associated with ulcerative colitis. Furthermore, the clinical and histological characteristics of 18
previously reported cases are summarized. This case series and literature review will encourage the accurate
diagnosis and treatment of esophageal ulcers associated with ulcerative colitis.

Key words: ulcerative colitis, esophageal ulcer, manifestation

(Intern Med Advance Publication)

(DOI: 10.2169/internalmedicine.4437-20)

Introduction Case Report

Ulcerative colitis (UC) is primarily a disease of the colon;

however, extracolonic manifestations have been described.
Extracolonic manifestations particularly involve the blood,
joints, skin, biliary tracts, liver, kidneys, lungs, and upper di-
gestive tract (1). Gastroduodenitis associated with UC
(GDUC) has been noted in 7.6% of severe cases of
UC (2, 3), making it a common extracolonic manifestation
of UC. In contrast, there have been relatively few reports of
esophageal ulcer occurring as an extracolonic manifestation
of UC (4).
We herein report two cases of UC complicated with
esophageal ulcers. Furthermore, we review 18 previously re-
ported cases of esophageal ulcers associated with UC. We
summarize these cases to help characterize esophageal ulcer
occurring as a complication of UC.
Case 1
A 16-year-old girl presented with chest pain and diarrhea
with blood and mucus. No oral, genital ulcers or skin le-
sions were evident. Esophagogastroduodenoscopy showed an
ulcer with aphthae in the esophagus (Fig. 1a) and diffuse
aphthae in the stomach (Fig. 1b). A histological examination
of the esophageal ulcers showed severe inflammatory cell
infiltration (Fig. 1d), and the gastric erosions revealed fo-
cally enhanced gastritis. Colonoscopy revealed superficial
ulcers and mucosal friability (Fig. 1c) from the rectum to
the cecum. The terminal ileum was normal. In the histologi-
cal examination, inflammatory cell infiltration with cryptitis
was detected in the sigmoid colon and rectum (Fig. 1e);
therefore, pancolitis-type UC was diagnosed comprehen-
sively.
She was not taking any medicine, including non-steroidal
anti-inflammatory drugs, and Helicobacter pylori infection
was not confirmed. A serological examination of viral infec-

１
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Japan and ２ Niigata Daigaku Chiiki Iryo Ky-
oiku Center Uonuma Kikan Byoin, Department of Gastroenterology and Hepatology, Japan
Received: January 8, 2020; Accepted: March 27, 2020; Advance Publication by J-STAGE: May 23, 2020
Correspondence to Dr. Atsunori Tsuchiya, atsunori@med.niigata-u.ac.jp

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 Intern Med Advance Publication DOI: 10.2169/internalmedicine.4437-20

(a) (b)

(c) (d) (e)

Figure 1. Esophagogastroduodenoscopy, colonoscopy, and their pathological findings. (a) Esopha-

gogastroduodenoscopy showing an ulcer with aphthae (arrows) in the mid intrathoracic esophagus.
(b) Esophagogastroduodenoscopy showing widespread aphthae (arrowheads) at the antrum. (c) Colo-
noscopy showing erythema and mucosal friability in the sigmoid colon. (d) Biopsy specimen from the
esophageal ulcers showing severe inflammatory cell infiltration [Hematoxylin and Eosin (H&E) stain-
ing, ×100]. (e) Biopsy specimen from the colon showing inflammatory cell infiltration with cryptitis in
the rectum (H&E staining, ×100).

tions (varicella zoster virus, herpes simplex virus, cytomega-
lovirus, and Epstein-Barr virus-DNA) was also negative.
Therefore, esophageal ulcers and gastroduodenitis associated
with UC (GDUC) were diagnosed.
Treatment with intravenous prednisolone (60 mg/day) was
started, and her chest pain and diarrhea were resolved in a
few days. Esophagogastroduodenoscopy on the seventh day
showed healing of the esophageal ulcers (Fig. 2a) and gas-
troduodenal aphthae (Fig. 2b). Colonoscopy showed im-
provement in the inflammation of the colon (Fig. 2c). She
has experienced no relapse for two years.
Case 2
A 19-year-old woman was admitted to our hospital due to
bloody stool and chest pain on swallowing. She was not tak-
ing any medication. Laboratory tests showed hypoalbumine-
mia, mild anemia and inflammatory responses: total protein
(6.9 g/dL), albumin (2.8 g/dL), hemoglobin (10.1 g/dL),
white blood cell (4,140/mm3), mild neutrophilic leukocytosis
(61.6%), thrombocytosis (platelets 28.9×104/μL), and in-
creased C-reactive protein levels (6.88 mg/dL). Stool cul-
tures were normal. Serological assays for viruses, including
herpes simplex, cytomegalovirus, varicella, and Epstein-Bar
did not demonstrate primary infection. Because of her
mouth and chest pain symptoms, esophagogastroduodeno-
scopy was performed, showing a longitudinal ulcer in the
lower esophagus (Fig. 3a) and oral ulcers. Histologic find-
ings showed infiltration of inflammatory cells in the epithe-
lia (Fig. 3d). Colonoscopy showed superficial ulcers and
mucosal friability (Fig. 3b) in the entire colon, from the rec-
tum to the cecum. We also detected mucosal friability in the
terminal ileum (Fig. 3c). The histologic findings here
showed inflammatory cell infiltration with basal plasmacyto-
sis in the transverse colon and inflammatory cell infiltration
with cryptitis in the rectum (Fig. 3e). She was diagnosed
with esophageal ulcer complicated with pancolitis-type UC
comprehensively.
Induction therapy was started with intravenous predniso-
lone (50 mg/day). Thereafter, her bloody stool and pain on
swallowing improved within one week. Esophagogastroduo-
denoscopy after four weeks showed healing of the oral and
esophageal ulcers (Fig. 4a). Colonoscopy after four weeks
also showed complete remission (Fig. 4b). She has shown
no relapse of esophageal lesions for one year.
Discussion
In 1961, Margoles et al. (5) first reported a case of

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 Intern Med Advance Publication DOI: 10.2169/internalmedicine.4437-20

(a) (b)

(c)

Figure 2. Esophagogastroduodenoscopic and colonoscopic findings. (a) EGD showing marked

healing of the esophageal ulcers (arrows). (b) EGD showing healing of the gastroduodenal aphthae.
(c) Colonoscopy showing improvement of mucosal edema and vascular appearance of the sigmoid
colon.

pancolitis-type UC with esophagitis. There have been 18 re-
ported cases of esophageal ulcers associated with UC, and
we encountered 2 new cases ourselves. The previously re-
ported cases of esophageal ulcers associated with UC (Case
3 to 20) and our new cases (case 1 and 2) are summarized
in Tables 1-3.
We reviewed these 20 cases and summarized their find-
ings in Table 1 (4-16). The average age of the patients was
28.2 years (range 14-53), and the ratio of men to women
was 14: 6. The duration of UC was from 0 to 21 years.
There were 13 cases of pancolitis, 3 cases of left-side coli-
tis, 1 case of right-side colitis, and 3 cases with unknown
details. Seven of the 18 cases had esophageal ulcers at the
onset of UC, and 2 cases had ulcers at the time of UC re-
lapse. Two cases were in UC remission, and 7 cases oc-
curred after total colectomy. According to the review results,
esophageal ulcer complications were relatively common in
the young compared with the elderly. Furthermore, esopha-
geal ulcer was often complicated in patients at the onset of
colitis, or at the time of relapse. It has been reported more
aggressive UC entities, such as active pancolitis, may be re-
lated to the development of gastroduodenitis associated with
UC (GDUC) (2). Furthermore, cases of esophageal ulcers
after surgery indicate UC may not be resolved in other or-
gans, even after total colectomy (3).
Of the 20 cases, there were 4 cases of multiple esopha-
geal ulcers. There were two cases of entire esophageal ulcer,
five of mid-esophageal ulcer, two of lower to middle
esophageal ulcer, and five with unknown details. Endoscopic
findings of esophageal ulcer complicated with UC were dif-
ferent from GDUC. While GDUC was defined as friable and
granular mucosa (2, 3), esophageal ulcer complicated with
UC is a punched-out ulcer and mostly occurs in the middle
to the lower esophagus.
Regarding the pathology, in all cases described, only non-
specific inflammatory cell infiltration was observed, with no
UC-specific findings reported. Although the relationship be-
tween the esophageal ulcers and UC was not confirmed his-
tologically, no other causes of esophageal ulcers were identi-
fied, and treatment for UC was also effective for the esopha-
geal lesions. Regarding treatment, 10 cases were treated
with prednisolone, and 2 cases received 5-aminosalicylate.
GDUC is treated with medications similar to those used for
UC (3, 17) and is more responsive to treatment, showing
less frequent relapse than colitis. Our two newly reported
cases followed a similar course.
Of the 18 reported cases, 45% had other complications,
namely oral lesions in 7 cases, skin lesions in 6 cases, ar-
thritis in 3 cases, and pancreatitis in 1 case. The case re-
ported by Knudsen and Sparberg (6) had a generalized
maculopapular eruption as a complication associated with
pancolitis-type UC. The patient reported by Rosendorff (7)

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 Intern Med Advance Publication DOI: 10.2169/internalmedicine.4437-20

(a) (b)

(c) (d) (e)

Figure 3. Esophagogastroduodenoscopy, colonoscopy, and their pathological findings. (a) EGD

showing a longitudinal ulcer in the lower esophagus. (a) Colonoscopy showing mucosal friability in
the rectum. (c) Colonoscopy showing mucosal friability in the terminal ileum. (d) Biopsy specimen
from the esophageal ulcers showing infiltration of inflammatory cells in the epithelia [Hematoxylin
and Eosin (H&E) staining, ×100]. (e) Biopsy specimen from the rectum showing inflammatory cell
infiltration with basal plasmacytosis and cryptitis (H&E staining, ×100).

(a) (b)

Figure 4. Esophagogastroduodenoscopic and Colonoscopic findings. (a) EGD showing healing of

the esophageal ulcers. (b) Colonoscopy showing remission of the rectum.

had buccal ulceration and arthritis. Most cases of UC with
esophageal ulcer have had other extracolonic manifestations.
Various extracolonic manifestations of UC, such as ocular
lesions, skin disease, and peripheral arthritis, have been re-
ported (1); however, their causes are currently unknown.
In conclusion, esophageal ulcer associated with UC is ex-
tremely rare. In most cases, it may occur as an extracolonic
manifestation. The pathological findings of esophageal le-
sion are non-specific for UC. Therefore, a comprehensive di-
agnosis excluding disorders related to infection and medica-
tion is required. UC-associated esophageal ulcers are typi-
cally associated with the disease onset or relapse of UC.
particularly in younger patients, and the treatment response
is fortunately considered good. However, the etiology of

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 Intern Med Advance Publication DOI: 10.2169/internalmedicine.4437-20

Table 1. Clinical Data of UC Patients with Esophageal Ulcer.

Case Ref Age Duration

Authors Sex UC phase Type UC treatment
(No) No. (yrs) of UC
1 Ours 16 F 0 Active Total PSL
2 Ours 19 F 0 Active Total PSL
3 6 Knudsen KB 15 M 2 years Remission Left side PSL, SASP
4 7 Rosendorff C 23 M 5 years Remission Total PSL, SASP
5 8 Christopher NL 21 F 0 Active N/A PLS, SASP
6 19 M 0 Active N/A N/A
7 10 Konishi 47 F 0 Active Right side 5ASA
8 4 Asakawa 18 F 7 years Relapse Active Total SASP
9 11 Ikeda 18 M 1 year Active Left side PSL, 5ASA
10 12 Higashi 19 M 0 Active Total none
11 13 Sato 51 M 0 Active Total PSL, 5ASA
12 14 Ose 33 M 0 Active Total PSL, LCAP
13 15 Izawa 52 F 3 years Relapse Active Left side SASP
14 5 Margoles JS 28 M 17 years Post operation Total Total colectomy and ileostomy
15 8 Christopher NL 26 M 2 months Post operation Total Sbtotal colectomy and ileostomy
16 14 F 5 years Post operation Total Sbtotal colectomy and ileostomy
17 24 M 9 years Post operation Total Total proctocolectomy
18 9 Howard 21 M 3 years Post operation Total Total colectomy and ileostomy
19 16 Kuroki 47 M 21 years Post operation N/A Sbtotal colectomy and ileostomy
20 53 M N/A Post operation Total Sbtotal colectomy
UC: ulcerative colitis, N/A: data not available, PSL: prednisolone, SASP: salazosulfapyridine, 5-ASA: 5-aminosalicylic acid

Table 2. Clinical Data of UC Patients with Esophageal Ulcer.

Case
Esophagial ulcer(EU) Location EU symptoms
(No)
1 An esophageal ulcer with aphthae Middle esophagus Chest pain
2 Longitudinal oesophageal ulcer Lower esophagus Chest pain on swallowing
3 Severe esophagitis Lower esophagus Parasternal chest pain and dysphagia
4 Shallow ulceration with gross diffuse irregularity Middle and lower esophagus Dysphagia
and polyp formation
5 Active ulcerative esophagitis N/A N/A
6 Marked ulcerative esophagitis N/A Substenal pain and dysphagia
7 Multiple irregular esophageal ulcers Whole esophagus Anterior chest pain and dysphagia
8 Longitudinal oesophageal ulcer with haemorrhage Middle and lower esophagus Sore throat and pain on swallowing
9 Punched-out esophageal ulcer Middle esophagus Sore throat and anterior chest pain
10 Punched-out esophageal ulcer Middle esophagus General fatigue
11 Punched-out esophageal ulcer Middle and lower esophagus Anterior chest pain on swallowing
12 Punched-out esophageal ulcer Middle and lower esophagus Anterior chest pain and dysphagia
13 Punched-out esophageal ulcer Middle esophagus Anterior chest pain on swallowing
14 Web formation Middle esophagus No
15 Esophagial ulcerations with perforaton into the N/A Dysphagia, fever, hypotension
anterior mediastinum
16 Necrotizing fibrinopurulent ulceration N/A N/A
17 Ulcerative and membranous esophagitis N/A Nausea, vomiting and hematemesis
18 Multiple friable ulcerations Whole esophagus Severe odynophagia and dyspahgia
19 Necrosis Lower esophagus Epigastric pain
20 Necrosis Middle and lower esophagus Hematemesis
UC: ulcerative colitis, N/A: data not available

esophageal ulcer associated with UC remains unknown. atypical aspects and require strict follow-up.
Since UC has various pathologies, the accumulation of more We believe that this case series and literature review will
cases will be necessary to confirm these findings in the fu- facilitate the accurate and prompt diagnosis of esophageal
ture. The two cases reported in the present study also had ulcer associated with UC.

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 Intern Med Advance Publication DOI: 10.2169/internalmedicine.4437-20

Table 3. Clinical Data of UC Patients with Esophageal Ulcer.

Case Outcome of
EU biopsy EU Treatment Other complication
(No) EU
1 Severe inflammatory cell infiltration PSL Improvement No
2 Infiltration of inflammatory cells in the PSL Improvement Oral ulcer
epithelia and no specific information
3 Superficial inflammation PSL Improvement Maculopapular eruption
4 Chronically inflamed and edematous, with PSL Improvement Buccal ulceration and arthritis
a dense infltrate of plasma cells,
lymphocytes, and histocytes
5 N/A - - No
6 N/A - - Necrotic ulceration in the inguinal,
genital regions and lower extremities
7 Nonspecific findings other than 5ASA, H2blocker Improvement No
inflammatorycell infiltration
8 Nonspecific findings other than PSL Improvement No
inflammatorycell infiltration
9 Nonspecific findings (Appearance of PSL Improvement Oral ulcer and pancreatitis
regenerative epithelium)
10 Nonspecific findings PSL, SASP Improvement No
11 Thickening of epithelial stratum spinosum PPI Improvement No
without nuclear inclusion body
12 Nonspecific findings (Appearance of PPI Improvement No
regenerative epithelium)
13 Nonspecific findings other than PSL Improvement No
inflammatorycell infiltration
14 N/A PSL N/A Mouth and pyoderma gangrenosum
15 N/A - - Oral ulcerations, pustular dermatitis,
arthritis
16 N/A - - N/A
17 N/A - - Ulcar of his buttock, paronychia of
hands
18 Dense infiltrate of polymorphonuclear cells, PSL, tetracycline N/A Arthritis, episcleritis, oral ulcerations
a few eosinophils and mononuclear cells and erythema nodosum
19 Inflammatory cell and infiltration PPI Stricture No
20 Not examination PPI Stricture No
UC: ulcerative colitis, EU: Esophageal Ulcer, N/A: data not available, PSL: prednisolone, SASP: salazosulfapyridine, 5-ASA: 5-aminosalicylic
acid, PPI: Proton pump inhibitor

The authors state that they have no Conflict of Interest (COI).
Acknowledgement
This work was supported by Takeda Japan Medical Office
Funded Research Grant 2018.
Disclosure: The authors declare that they have no current fi-
nancial arrangement or affiliation with any organization that may
have a direct influence on their work. Informed consent was ob-
tained from the patients for the publication of their information
and imaging.
Declarations
Ethics approval and consent to participate: The study was
reviewed and approved by the Institutional Review Board of Nii-
gata University.
Consent for publication: Written informed consent was ob-
tained from the patients for publication of these case reports and
accompanying images.
Competing interests: The authors declare that they have no
current financial arrangement or affiliation with any organization
which may have a direct influence on their work.
Author’s contributions: KT, AT, HS, TM and SM diagnosed
and drafted the manuscript. ST analyzed data. All authors criti-
cally reviewed the manuscript and approved the final draft.
Disclosure: The authors declare that they have no current fi-
nancial arrangement or affiliation with any organization which
may have a direct influence on their work.
References
1. Greenstein AJ, Janowits HD, Sachar DB. The extra-intestinal com-
plications of Crohn’s disease and ulcerative colitis: a study of 700
patients. Medicine (Baltimore) 55: 401-412, 1976.
2. Hori K, Ikeuchi H, Nakano H, et al. Gastroduodenitis associated
with ulcerative colitis. J Gastroenterol 43: 193-201, 2008.
3. Hisabe T, Matsui T, Miyaoka M, et al. Diagnosis and clinical
course of ulcerative gastroduodenal lesion associated with ulcera-
tive colitis: possible relationship with pouchitis. Dig Endosc 22:
268-274, 2010.
4. Askawa A, Kojima Y, Fujii E, et al. Case of Ulcerative Colitis As-
sociated with Oesophageal Ulcer. J Int Med Res 28: 191-196,

6
 Intern Med Advance Publication DOI: 10.2169/internalmedicine.4437-20

2000. colitis combined with esophageal ulcer. Journal of Japan Surgical

5. Margoles JS, Wenger J. Stomal ulceration associated with pyo-
derma gangrenosum and chronic ulcerative colitis. Report of two
cases. Gastroenterology 41: 594-598, 1961.
6. Knudsen KB, Sparberg M. Ulcerative oesophagitis and ulcerative
colitis. JAMA 201: 140, 1967.
7. Rosendorff C, Grieve NW. Ulcerative oesophagitis in association
with ulcerative colitis. Gut 8: 344-347, 1967.
8. Christopher NL, Watson DW, Farber ER. Relationship of chronic
ulcerative oesophagitis to ulcerative colitis. Ann Intern Med 70:
971-976, 1969.
9. Haward MZ, Gilbert R, Simmy B. Apthous ulcers of the esopha-
gus in a patient with ulcerative colitis. Gastrointestinal Endoscopy
30: 298-299, 1984.
10. Konishi H, Mitsuhashi Y, Fujino N, et al. A case of right-sided ul-
cerative colitis associated with unusual esophageal ulcer. Chiba
Medical Association Magazine 50: 143-144, 1998.
11. Ikeda Y, Yonezawa K, Suzuki K, et al. A case of ulcerative colitis
associated with a hemorrhagic esophageal ulcer. Journal of
Kushiro City Gen 12: 129-133, 2000.
12. Higashi Y, Nakamura T, Sunayama K, et al. A case of ulcerative
Association 65: 143-146, 2004.
13. Sato N, Kurakata H, Hirano N, et al. A case of ulcerative colitis
combined with esophageal ulcer. Progress of Digestive Endoscopy
65: 2004.
14. Ose T, Ishihara S, Oshima N, et al. A case of ulcerative colitis
complicated with giant esophageal ulcer. Clinics in Gastroenterol-
ogy 11: 93-96, 2005.
15. Izawa N, Sugaya T, Kanamori A, et al. A case of ulcerative colitis
with esophageal ulcer. Progress of Digestive Endoscopy 87: 2015.
16. Kuroki H, Sugita A, Koganei K, et al. Two cases of esophageal ul-
cer after surgical treatment for ulcerative colitis. Clin J Gastroen-
terol 2019.
17. Chiba M, Ono I, Wakamatsu H, Wada I, Suzuki K. Diffuse gastro-
duodenitis associated with ulcerative colitis: treatment by inflixi-
mab. Dig Endosc 25: 622-625, 2013.
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